Effect of MDR1 C1236T polymorphism on cyclosporine pharmacokinetics: A systematic review and meta-analysis.

Abstract

Background:Cyclosporine (CsA) is one of the immunosuppressive drugs, whose pharmacokinetic characteristics vary greatly among individuals. The published data reveal conflicting effects of the polymorphism of MDR1 exon 12 SNP C1236T on the pharmacokinetics of cyclosporine.This study aims to conduct a meta-analysis to investigate the effect of SNP C1236T on the pharmacokinetics of cyclosporine.Methods:A literature retrieval was conducted to find the relevant papers in databases including PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wan Fang Database (Wan Fang), Chinese Biomedical Literature Database (CBM), VIP Database for Chinese Technical Periodicals (VIP) electronic source for published studies until January 2017. The pharmacokinetic parameters, including C0 (trough blood concentration), C2 (whole-blood levels at 2 hours after drug intake), Cmax (the maximum concentration), and daily dose were extracted and a meta-analysis was performed by RevMan 5.3.Results:A total of 11 papers concerning 1361 individuals were included in the meta-analysis. As for dose adjusted C0, the results showed difference between subjects carrying CC genotypes and TT genotypes (MD: 6.76, 95% CI [2.38, 11.14], P = .02]. As for C2, the results showed significant difference between subjects carrying CC genotypes and CT genotypes (MD: −18.50, 95% CI [−35.49, −1.52], P = .03), as well as CC genotypes and TT genotypes (MD: −19.01, 95% CI (−35.85, −2.16), P = .03). As for Cmax, daily dose, and C0, the overall results showed no major influence.Conclusions:MDR1 C1236T polymorphism may have a minor effect on cyclosporine pharmacokinetics in transplantation patients.